Foundation-model-guided radiogenomic discovery linking cancer genomes to cancer scans

The function of many genes is still unknown, and conventional driver-discovery methods, which rely on how frequently a gene is mutated, cannot assess genes that are only rarely affected. Here we pair Evo~2-based genome analysis with routine clinical imaging to identify gene--phenotype associations at genome-wide scale. For every somatic mutation across three TCGA cohorts (cRCC=clear cell renal cell carcinoma, HCC=hepatocellular carcinoma, and BC=breast cancer; $n = 340$ total), Evo~2 predicts a severity score, with no task-specific training. Per-gene severity summaries are then correlated with radiomic features extracted from paired tumor segmentations, controlling for total mutation burden. In TCGA-cRCC ($n = 162$), this sweep recovers established renal-cancer drivers and identifies 46 additional genes reaching false discovery rate (FDR) significance absent from curated cancer-gene panels, several of which are Mendelian ciliopathy and cytoskeletal-disease genes. These results demonstrate that pairing a genomic language model with widely available clinical imaging can serve as a hypothesis-free discovery tool for gene--imaging associations invisible to conventional approaches.

Bayesian uncertainty estimation improves clinical decision making in medical AI agents

Machine learning models for medical image analysis typically lack a reliable measure of confidence, limiting their use in ambiguous or atypical cases. Here we show that Monte Carlo dropout, applied to a multi-task chest-radiograph classifier (eight thoracic findings, 137,593 training images), provides an epistemic uncertainty signal that tracks generalisation across training-set scales and flags confident yet error-prone predictions. Adding this signal to the point prediction raised error-detection AUROC from 0.74 to 0.77 ($Δ$AUROC +0.023, 95% CI [+0.014, +0.033]). In a controlled 2x2 factorial experiment, a clinical-decision-support agent exploited this uncertainty only when it was delivered as a binary error-risk flag rather than as raw scores, cutting confident misdiagnoses on unreliable findings from 8.5% to 2.7%. Epistemic uncertainty estimation thus carries decision-relevant information beyond point predictions, but its value for downstream agents depends on how it is communicated.

MedicalPatchNet: A Patch-Based Self-Explainable AI Architecture for Chest X-ray Classification

Deep neural networks excel in radiological image classification but frequently suffer from poor interpretability, limiting clinical acceptance. We present MedicalPatchNet, an inherently self-explainable architecture for chest X-ray classification that transparently attributes decisions to distinct image regions. MedicalPatchNet splits images into non-overlapping patches, independently classifies each patch, and aggregates predictions, enabling intuitive visualization of each patch's diagnostic contribution without post-hoc techniques. Trained on the CheXpert dataset (223,414 images), MedicalPatchNet matches the classification performance (AUROC 0.907 vs. 0.908) of EfficientNet-B0, while substantially improving interpretability: MedicalPatchNet demonstrates substantially improved interpretability with higher pathology localization accuracy (mean hit-rate 0.485 vs. 0.376 with Grad-CAM) on the CheXlocalize dataset. By providing explicit, reliable explanations accessible even to non-AI experts, MedicalPatchNet mitigates risks associated with shortcut learning, thus improving clinical trust. Our model is publicly available with reproducible training and inference scripts and contributes to safer, explainable AI-assisted diagnostics across medical imaging domains. We make the code publicly available: https://github.com/TruhnLab/MedicalPatchNet

An Ordinal Regression Framework for a Deep Learning Based Severity Assessment for Chest Radiographs

This study investigates the application of ordinal regression methods for categorizing disease severity in chest radiographs. We propose a framework that divides the ordinal regression problem into three parts: a model, a target function, and a classification function. Different encoding methods, including one-hot, Gaussian, progress-bar, and our soft-progress-bar, are applied using ResNet50 and ViT-B-16 deep learning models. We show that the choice of encoding has a strong impact on performance and that the best encoding depends on the chosen weighting of Cohen's kappa and also on the model architecture used. We make our code publicly available on GitHub.